Conducting Compliance Assesments

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CONDUCTING COMPLIANCE ASSESSMENTS

Allen Ditch Director Corporate Quality Bristol
Myers Squibb Medical Research Summit March 6,
2003
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Agenda

• Types of Assessments
• Objectives
• Selecting the Site(s) to Audit
• Investigator Site Audit Follow-Up
• FDA Clinical Investigator Inspection

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Objectives

• Ensure rights safety of study subjects
• Ensure integrity of data
• Verify compliance with regulatory requirements
• Verify compliance with protocol requirements

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Selecting the Investigator Site To Be Audited

• Study Drug, Protocol or Project
• Number of Patients Accrued
• Complexity of Study
• Experience of the Investigator / Site
• History with the company (via monitors or audits)
• Experience of the monitor or CRO
• For Cause - concerns identified

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Preparing for the Investigator Site Assessment

• Notify the internal clinical group (monitor /
  medical monitor)
• Discuss plans and process with internal clinical
  group
• Request data base, CRFs, regulatory documents
• Conduct In-House audit
• Request specific charts depending on the
  situation
• Clinical Group arranges the assessment visit
• Conduct the assessment

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Conducting the Investigator Site Assessment

• Interview responsible site personnel - confirm no
  changes since last monitoring visit or study
  start
• Review regulatory study file
• Compare CRF entries to source records
• Confirm any deviations
• Assess Pharmacy - records, storage
• Assess any special requirements - freezer,
  diagnostic equipment

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INTERVIEW STAFF

• Verify involvement of the investigator
• Verify responsibilities delegated
• Review informed consent process
• Review other systems implemented at investigator
  site

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STUDY FILE REVIEW

• Regulatory documents - FD1572, CVs, IRB
  composition, lab normals, financial disclosure
  statement ...
• Most recent consent form and all versions
• IRB approval and appropriate reapproval(s)
• Current protocol and all amendments
• Signature log - site staff
• Monitor log and correspondence
• Study specific
• Financial payments usually not reviewed

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SOURCE RECORD REVIEW

• Verify involvement of the investigator
• Who is doing what (consent, randomize, exams,
  dose adjustments)
• Confirm source records support dates and data in
  CRF
• Confirm all sources for records identified

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PHARMACY REVIEW

• Verify investigator involvement
• Verify records are maintained and up-to-date
• Verify drug only dispensed to study subjects
• Verify storage conditions are appropriate
• Review Inventory supplies
• Preparation area (if appropriate)

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RED FLAGS - The watch out

• Subject registered or examined on holiday/weekend
• Subjects seen when physician is not in the office
• New concomitant medicine no new adverse event
• No corrective action for known problems
• SAEs not in CRF
• Consent form irregularity
• Lack of study drug accountability
• Lab results repeating or rounded
• Everything is too perfect ???

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Post - Assessment Follow-Up

• Wrap-up discussion with site staff
• summarize processes found in compliance
• review anything requiring corrective action
• Audit report written and addressed to clinical
  area
• Action Plan to address findings in established
  time frame
• Open items followed by audit team until closure

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FDA INSPECTIONS

• NDA support vs. for cause
• Standard format / process
• Inspection results are available through FOI
• Warning Letters posted on the FDA Home Page
• FDA Compliance Program URL www.fda.gov/ora/compli
  ance_ref/bimo/7348_811/default.htm

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QUESTIONS DISCUSSION